Radium Isotope Improves Prostate Cancer Survival

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This study evaluated the efficacy of radium-223 in a phase III, randomized, double-blind, placebo-controlled study in men with castration-resistant prostate cancer and bone metastases who were not eligible to receive, or declined docetaxel.

Radium-223, as compared with placebo, significantly improved overall survival and was associated with low myelosuppression rates and fewer adverse events.

A variant of radium, the element that killed Marie Curie, prolongs survival in men with castration-resistant prostate cancer that has spread to the bone, researchers said.

In a randomized phase III trial, men getting radium-223 had a 30% reduction in their risk of death compared with men getting placebo, according to Christopher Parker, MD, of the Royal Marsden Hospital in Sutton, England, and colleagues.

The isotope, now marketed as Xofigo, was also associated with fewer adverse events, Parker and colleagues reported in the July 18 issue of the New England Journal of Medicine.

The industry-sponsored trial was stopped early after an interim analysis showed a clear survival benefit for the radium isotope.

Like radium-226, discovered by Curie, radium-223 emits alpha particles that cause DNA damage. A key difference is the half-life -- 1,600 years in the case of radium 226 and 11.4 days for radium-223. As well, the body treats the element in much the same way as calcium; both migrate to bones.

That "winning combination" of properties makes radium-223 a new anticancer weapon, commented Neha Vapiwala, MD, and Eli Glatstein, MD, both of the University of Pennsylvania in Philadelphia.

The study "imparts some long-awaited momentum to research on the use of alpha emitters and shows an overall survival advantage with a compound that is safe and manageable for both patients and providers," they argued in an accompanying editorial.

Exactly how the substance will be used remains an open question, but they added it's likely that "radium-223 will both complement and contend with existing therapies."

For patients like those in the study, "we have a number of options that are not that effective," commented Chandan Guha, MBBS, PhD, of Albert Einstein College of Medicine and Montefiore Medical Center in New York City.

The trial is one of the first to show a survival benefit, he told MedPage Today, and it's also important that the study found radium to be "highly safe."

On the other hand, he cautioned, physicians will likely want to use the element in combination with other drugs, and "combination trials have to be seen" before that can happen.

Parker and colleagues noted that an early stage trial, combining radium-223 with docetaxel, is underway.

In the pivotal trial, they reported, 921 participants were randomized in a 2-to-1 fashion to get radium or placebo, combined with the best available standard care.

The primary endpoint was overall survival, with a key secondary efficacy endpoint of time to the first symptomatic skeletal event. The interim analysis, conducted when 314 deaths had occurred, found a median 14-month survival for the radium group compared with 11.2 months for those getting placebo, a difference that was significant at P=0.002.

In the journal, Parker and colleagues reported an updated analysis, performed when 528 deaths had occurred but before any patients had crossed over from placebo to radium-223.

The analysis included all 921 patients and confirmed the survival benefit -- a median overall survival of 14.9 months for radium patients and 11.3 months for those in the placebo group.

In the radium-223 group, 54% of patients died (333 of 614), compared with 64%% of those getting placebo (195 of 307). The difference yielded a 30% reduction in the hazard ratio, which was significant (P<0.001).

The median time to first symptomatic skeletal event was also significantly improved (P<0.001) for the radium group, the researchers reported -- 15.6 months versus 9.8 months.

The proportion of patients reporting adverse events after getting the study drug was "consistently lower" in the radium-223 group -- 93% versus 96%. The same was true for grades 3 or 4 adverse events, serious adverse events, and discontinuation because of adverse events, Parker and colleagues reported.

The study had support from Algeta and Bayer HealthCare Pharmaceuticals. Parker reported financial links with Amgen, Astellas, Bayer, Janssen, Bristol-Myers Squibb, BN ImmunoTherapeutics, Takeda, and sanofi-aventis. Several authors are employees of the sponsors.

The editorial authors did not report any financial links with industry.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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